Study reference

Study characteristics

Patient characteristics ²

Outcome measures and effect size ⁴

Comments

Bonner, 2018

Type of study: qualitative

Study method: semi-structured interviews, analysed by framework analysis

Country: Australia

Inclusion criteria: adult first-degree at-risk relatives of a person with HCM

N total at baseline: 32

G+/F-: 20

G?/F-: 4

G+/F+: 4

G-/F-: 4

Age: 20-69

Sex: 25% M/75% F

 Key themes were as follows:

(1) helping the next generation,

(2) misunderstanding risk,

(3) discrepancy between actual/perceived impact.

Participants described multiple psychological (shock, worry, uncertainty) and behavioural (career, sport,

insurance, family planning) consequences, depending on perceived risk. Most considered only the benefits of genetic testing for children or grandchildren, but there were some cases of significant adverse impact.

The interpretation of the HCM genetic test result is variable for silent gene carriers and can lead to psychological and behavioural changes.

The impact of a positive gene result may be mitigated by increased clarity of the clinical consequences and efforts to ensure informed decision-making, highlighting even further the important role of cardiac genetic counselling.

Burns, 2017

Type of study: qualitative

Study method: semi-structured interviews, analysed by framework analysis

Country: Australia

Inclusion criteria: HCM probands attending a multidisciplinary specialised HCM clinic in Sydney,

Australia who underwent genetic testing and had either (1) a pathogenic or likely pathogenic HCM variant, (2) a VUS or (3) no variant identified.

N total at baseline:

19

Important prognostic factors²:

Age: 54±13

Sex: 11 M/ 8 F

Probands were more concerned with their clinical diagnosis than gene result and in some, recall and understanding of genetic diagnosis was poor. Several participants expected genetic testing would

alleviate uncertainty, often holding an altruistic view of participation in testing, removing their sense of self and failing to appreciate fully the familial implications.

With the key utility of HCM genetic testing and counselling being for greater risk prediction for at-risk relatives, effective communication within the family is critical. While communication appeared adequate, further questioning found it was often vague, failing to translate into meaningful action by relatives.

Christiaans, 2010

&

Christiaans 2009b

Type of study: cross-sectional study

Study method: survey

Country: The Netherlands

Inclusion criteria: All HCM mutation carriers counseled and tested for an autosomal dominant single pathogenic mutation at our outpatient clinic were invited. Participants had received their DNA test result at least eighteen months ago, had to master Dutch, and were at least 16 years of age.

N total at baseline:

228

Important prognostic factors²:

age ± SD: 49 ± 15 years

Sex: 49% M / 51% F

Response rate: 228/264 questionnaires (86%)

Experiences with insurance

66/228 (29%) carriers applied for insurance (insurance for life, disability, health or funeral, pension or surviving relatives pension) of whom 39/66 (59%) reported problems (59%) during an average follow-up of 3 years since the DNA test result.

More problems were encountered by carriers with manifest disease (P=0.001) and carriers with symptoms of HCM (P=0.049).

Carriers identified after predictive DNA testing less frequently experienced problems (P=0.002).

Three carriers without manifest HCM reported problems (5% of applicants).

Frequently reported problems were higher premium (72%), grant access to medical records (62%), and complete rejection (33%).

Quality of life and psychological distress

Levels of quality of life and distress were not impaired compared to the Dutch population. Quality of life and distress were worst in carriers with manifest

HCM before DNA testing and best in predictively tested carriers without HCM. The latter group had even significantly better quality of life than the general population.

Illness and risk perception related variables were major determinants of quality of life and distress.

Christiaans, 2009

Type of study: cross-sectional study

Study method: survey

Country: The Netherlands

Inclusion criteria:

All HCM mutation carriers counseled at our outpatient clinic were invited to participate. DNA testing had to

occur in a predictive setting—all were asymptomatic relatives at the time of genetic counseling and DNA testing—and disclosure of their DNA test

result had occurred at least 18 months ago. Predictive

genetic counseling and testing are performed using adapted

Huntington guidelines, that is, psychosocial care and time for

reflection are not obligatory and the test result can be disclosed

by telephone or mail. Participants had to be Dutch speaking and at least 16 years of age.

N total at baseline:

123

Important prognostic factors²:

age: mean 47

Sex: 42% M/58% F

Response rate: 123/143 (86%)

Predictive genetic counseling and DNA testing were

evaluated on four domains: information provision, satisfaction with counseling, social pressure in DNA testing and regret of DNA testing.

Opinions on cardiac follow-up were assessed pertaining to communication, nervous anticipation, reassurance, and general disadvantages.

Genetic counseling was valued positively and only four carriers would rather not have known that they were a mutation carrier.

A majority received their DNA test result by mail or telephone, and almost all were satisfied.

Only 76% of carriers received regular cardiac follow-up. Those who did, had a positive attitude regarding the cardiac visits. General disadvantages of the visits were valued as low, especially by older carriers, men and carriers with manifest HCM.

Geelen 2011

Type of study: qualitative study

Study method: Semi-structured interviews, empirical analysis

Country: The Netherlands

Inclusion criteria:

N total at baseline:

57 members of 6 Dutch extended families involved in genetic testing for HCM.

Important prognostic factors²:

For example

age ± SD:

I:

C:

Sex:

I: % M

C: % M

Groups comparable at baseline?

Follow-up: 3,5 year

Reasons for fear of genetic discrimination

Results show that fears of genetic discrimination do not so much stem from the opportunity of genetic testing but much more from earlier experiences of discrimination of diseased family members.

How child’s best interest is constructed

Results show the best interest of a child is constructed via long-term processes in the broader context of family and kin. In this context, ‘‘best interests’’ are considered and reconsidered. We conclude that a child’s best interest should not be framed as the result of an instantaneous agreement between parents and professionals. In dealing with genetic testing of children, parents as well as professionals reflect on and learn from the processes of generating new meanings of ‘‘best interest.’’

Family work

Analysis shows that genetic testing does affect families, but that families perform a lot of ‘balancing work’ in order to prevent genetic testing from becoming too all-encompassing. There is much more continuity in family life than is often thought. Moreover, since these families show different styles of ‘family work’, establishing a single norm of ‘good communication’ in clinical genetics might in fact be more harmful for family life than genetic testing itself.

Ingles, 2012

Type of study: cost-effectiveness study

Study method: probabilistic Markov decision model

Country: Australia

Inclusion criteria: Clinical data that informed the transition variables were sought from the Australian National Genetic Heart Disease Registry, from available literature and in some cases where data were lacking, expert opinion was used.

Costs were from a thirdparty payer perspective, and were sought from the Australian National Hospital Cost Data Collection Report Round 12

(2007-8) and Australian Medicare Benefits Schedule.

Cost-effectiveness of the addition of genetic testing to HCM family management, compared to clinical screening alone.

The incremental cost-effectiveness ratio (ICER) was €587 per quality-adjusted life-year gained, and €9509) per additional life-year gained, making genetic testing a very cost-effective strategy.

Sensitivity analyses showed that the cost of proband genetic testing was an important variable. As the cost of proband genetic testing decreased, the ICER decreased and was cost savingwhen the cost fell below €185. In

addition, the mutation identification rate was also

important in reducing the overall ICER, although even at

the upper limits, the ICER still fell well within accepted

willingness to pay bounds.

Ingles, 2012b

Type of study: longitudinal study

Study method: survey

Country: Australia

Inclusion criteria: Clinically affected individuals and first-degree relatives at risk of a genetic heart disease aged more than 15 years.

N total at baseline: 54 (33 probands, 21 asymptomatic relatives)

Important prognostic factors²:

Age: mean 40-52

Sex: 25 M / 29 F

SF-36 for measuring health related quality of life was administered before genetic result and 1, 3, 6 and 12 months after the result was given.

Physical and mental component scores analyzed at baseline and 1–3 months were found to be unchanged in

all groups. Furthermore, no significant differences were observed up to 12 months after result.

About genetic testing for inherited heart diseases including HCM (35/54), but also other diseases.

Macleod, 2014

Type of study: qualitative study

Study method: telephone interview, using Interpretative Phenomenological Analysis

Country: UK

Inclusion criteria: young people who had a predictive test aged 15–25

years at the Clinical Genetic Service, Manchester, for HD, HBOC (BrCa 1 or 2) or FCM (Hypertrophic Cardiomyopathy or Dilated Cardiomyopathy)

N total at baseline: 36 (10 HCM)

Important prognostic factors²:

HCM group

Age: range 15-24

Sex: 5M / 5F

None of the participants expressed regret at having the test at a young age. Participants saw the value of pretest

counselling not in facilitating a decision, but rather as a source of information and support. Differences emerged among the three groups in parent/family involvement in the decision to be tested. Parents in FCM families were a strong influence in favour of testing

10/36 HCM. Other participants were tested for Huntington’s disease or hereditary breast and ovarian cancer

Ormondroyd, 2014

Type of study: qualitative study

Study method: in depth interviews, analysed using an inductive, thematic approach

Country: UK

Inclusion criteria: individuals who had undergone pre symptomatic genetic testing, but not within the preceding 6 months, and were aged over 18 years at the time of invite.

N total at baseline: 22 (18 HCM,

4 LQTS)

Important prognostic factors²:

Sex: 9 M / 13 F

Risk is perceived to be low pre-test in the absence of symptoms, and participants frequently test with the aim of ruling out risk to self and children. \

Testing of children is a complex decision; although older participants have concerns about possible adverse effects of genetic testing early in the life course, young participants are pragmatic about their result.

The meaning of a positive genetic test result may be difficult to conceptualise in the absence of clinical evidence of disease, and this may deter further

dissemination to at-risk family members.

A majority of participants see advantages in direct contact from health professionals as an alternative to family-mediated dissemination and support it in principle.

Implications for practice include

- addressing risk perception pre-test

- presenting genetic test information as part of a risk stratification process rather than a binary outcome.

Families may require more support or intervention in cascading genetic test information.

18/22 HCM

Smart, 2010

Type of study: qualitative study

Study method: semi-structured interviews

Country: UK

Inclusion criteria: had undergone a DNA test for an inherited cardiac condition, with diversity sought on differences in the condition (HCM/

LQTs), route into testing (proband/cascaded) and test result

(positive/negative).

N total at baseline: 27 (14 HCM, 13 LQTS)

the majority of participants in this sample embraced testing and screening as a way of providing health information for themselves or their relatives (particularly children).

There was nevertheless evidence of ambivalence about the value and impact of the DNA test information which could influence participants’ dispositions toward testing, and play into dilemmas about family communication.

Other concerns arose in relation to communicating about these disorders, decisions to involve elderly relatives and pressures relating to family responsibility.

The evidence of ambivalence provides insight into why some people may be resistant to testing, screening and

sharing information.

The findings about communication

processes indicate potential areas of concern for the

cascading process.

14/27 HCM

Spanaki, 2016

Type of study: cross-sectional

Study method: survey

Country: UK

Inclusion criteria: children and adolescents aged 3-18 years or

younger attending the hypertrophic cardiomyopathy clinic between October, 2006 and November, 2007

N total at baseline: 152

Important prognostic factors²:

Age (mean ± SD): 12 ± 3

Sex: 95 M / 57 F

Group A: had hypertrophic

cardiomyopathy

N=21 (14%)

Group G: harboured hypertrophic cardiomyopathy-causing sarcomeric mutations with normal echocardiograms

N= 23 (15%)

Group S: had a family history of hypertrophic

cardiomyopathy with normal investigations and attended for clinical cardiological screening

N= 108 (71%)

Children and parents completed the Generic Core Scales and Cardiac Module of the Paediatric Quality of Life Inventory (PedsQL) questionnaire as well as the Strengths and Difficulties Questionnaire to measure psychological well-being and quality of life of children.

Mean PedsQLTM total scores was significantly lower in HCM affected children (group A) compared to unaffected children. There was no significant difference between unaffected and gene-positive patients.

There was no significant difference between group S

and group G on any of the scales, or between the three groups of patients in the mean Strengths and

Difficulties Questionnaire scores.

Conclusion:

Children with hypertrophic cardiomyopathy have a

significantly reduced quality of life. Importantly, Quality-of-Life scores among unaffected children attending for

screening were not different compared with scores from a normative UK population

Wordsworth, 2010

Type of study: cost-effectiveness study

Study method: Economic decision model, using Treeage and a Markov model.

Country: UK

Inclusion criteria:

Information on the average number of children per family in the UK

was obtained from the Office of National Statistics and three different

family sizes simulated: one, two, or three children.

The natural history of each child was simulated using a Markov model

with the HCM health states being defined according to SCD risk.

All analyses were

from a UK hospital perspective.

2 diagnostic models were compared:

- Cascade clinical with five yearly repeat clinical investigation;

- Cascade genetic with five yearly clinical investigation for those whose parent’s DNA mutation was not identified.

The incremental cost per life year saved was €14 397 for the cascade genetic compared with the cascade clinical approach.

Genetic diagnostic strategies are more likely to be cost-effective than clinical tests alone. The costs for cascade molecular genetic testing were slightly higher than clinical testing in the short run, but this was largely because the genetic approach is more effective and identifies more individuals at risk.

Conclusion: The use of molecular genetic information in the diagnosis and management of HCM is a cost-effective approach to the primary prevention of SCD in these patients.

Wynn, 2018

Type of study: cross-sectional study

Study method: survey

Country: USA

Inclusion criteria: adult probands and relatives with a personal or family history of cardiomyopathy, including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM)

N total at baseline: 90

Important prognostic factors²:

age ± SD: 44 ± 13 (range 18-76)

Sex: 45 M / 45 F

Standardized psychological instruments including an adapted Multidimensional Impact of Cancer Risk Assessment (aMICRA), Impact of Event Scale (IES), and Satisfaction with Decision (SWD) scales were utilized.

Patients with positive genetic test results had higher scores for intrusive thoughts, avoidance, and distress when compared to those with negative genetic test results.

Patients with positive genetic test results were also more likely to make or plan to make life changes because of the results of their genetic testing.

Satisfaction with the decision to undergo genetic testing was similar regardless of genetic test results.

Including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM)